José Manuel Zozaya

Systemic and regional hemodynamics in patients with liver cirrhosis and ascites with and without functional renal failure

Systemic, femoral, and renal hemodynamics were evaluated in 7 control subjects and 20 cirrhotic patients with ascites, 14 of them without (group A) and 6 with (group B) functional renal failure. Hyperdynamic systemic circulation, increased plasma volume, and hyperreninism were present in groups A and B. These changes were more severe in group B, which showed, as compared with group A, lower total vascular resistances and mean arterial pressure together with increased cardiac index and plasma renin activity. Significant differences in regional hemodynamics were also observed between groups. In group A, femoral and renal fractions of cardiac output were respectively increased and reduced as compared with controls. By contrast, in group B, both fractions of cardiac output were reduced when compared either with controls or with group A. In the entire patient group there was a close direct correlation between femoral and renal fractions of cardiac output (r = 0.88; p less than 0.001) and both of them correlated independently with total vascular resistances (r = 0.79; p less than 0.001 in both cases). These results indicate that, in nonazotemic cirrhotics with ascites, vasodilatation in extrasplanchnic areas contributes to the genesis of the hyperdynamic circulation. The presence in group B of a reduced flow to extrasplanchnic territories, in association with an increase of the hyperdynamic circulatory status, suggests that exacerbation of splanchnic vasodilatation is involved in the development of the hepatorenal syndrome. Finally, in cirrhosis, the changes that occur in systemic hemodynamics appear to influence renal function and renal blood flow.

Spontaneous regression of hepatocellular carcinoma: a systematic review.

Objective To estimate the actual frequency of spontaneous regression of hepatocellular carcinoma. Methods A systematic review of the literature published during 1978–2007 has been carried out to identify randomized clinical trials of hepatocellular carcinoma that included a control arm receiving either placebo or best supportive care, and in which patients were followed prospectively for tumor response using predefined criteria. Data extraction was conducted independently by two investigators. A meta-analysis to provide a global estimation of regressions in the control arms was performed using an empiric Bayesian random-effects model. Results We identified 16 cases of regression (including minor and partial responses) in 10 phase III clinical trials. The rate of spontaneous objective partial regression among patients with hepatocellular carcinoma was 0.406% [95% confidence interval: 0.067–1.043%]. Conclusion Although very infrequent, spontaneous regression is not an extraordinary event among patients with hepatocellular carcinoma. Therefore, individual responses to any given therapy should be assessed with caution and this fact may be considered at the time of calculating sample size of pilot clinical trials of new agents.

Spontaneous Regression of Hepatocellular Carcinoma: Three Case Reports and a Categorized Review of the Literature

Hepatocellular carcinoma (HCC) is the most frequent form of primary liver cancer and the fifth most prevalent cancer worldwide [1]. Spontaneous tumor regression was first defined by Cole and Everson [2] as complete or partial clearance of malignant cells in the absence of any specific treatment, particularly antineoplastic chemotherapy. However, it may also occur during or after therapy, a situation in which therapy could be endorsed with an undeserved antitumor effect. Spontaneous tumor regression was at first thought to be an extremely infrequent phenomenon, with an estimated incidence of 1 in 60,000–100,000 cases [3]. Its mechanism is largely unknown, however, it has important implications in clinical research and clinical practice. The number of cases of spontaneous regression reported in the literature is higher in HCC than in other neoplasms [4], possibly reflecting a higher incidence. However, due to its exceedingly low frequency it would probably not affect the results of any study on HCC therapy. Following our observation of two cases of spontaneous regression and one case of sustained, complete regression in the course of a chemotherapeutic regimen with marginal efficacy in the treatment of this tumor, we have searched the cases published in the English literature and reviewed the possible mechanisms involved in such remarkable events. We have retrospectively reviewed all the cases recorded in our liver unit in which an objective tumor remission was observed that could not be convincingly ascribed to a therapeutic effect of any rational intervention. These consist of tumor ablation, any sort of embolizing procedure performed in the hepatic artery or its branches (including intra-arterial injection of Lipiodol for diagnostic or staging purposes), or pharmacological therapy that might have a known antiproliferative effect. Medical records of these patients were thoroughly reviewed trying to find any possible event that may have triggered the observed remission.

Transjugular intrahepatic portosystemic shunts using the Wallstent prosthesis: A follow-up study

AbstractPurpose: The aim of the present study was to assess the efficacy of transjugular intrahepatic portosystemic shunts (TIPS) in 45 patients with cirrhosis during a mean follow-up of 7 months. Methods: Forty-five consecutive patients treated by TIPS and who had been followed for at least 6 months after TIPS or until death, were included. Mean follow-up was 7.2±5.0 months. Shunt patency was assessed at 1 week and 1 month, then every 3 months after the procedure by Doppler US and angiography whenever needed. Results: Thirty-six patients had been stented for refractory bleeding from ruptured esophagogastric varices. Of these, 8 patients (22%) rebled, 7 of whom were treated by a second shunt. Nine patients were treated for refractory ascites. Three patients had recurrent ascites due to shunt obstruction. All were treated by a second shunt which occluded in 2 patients. As a whole, 14 (31.1%) patients developed shunt obstruction within a mean of 120±136 days, 4 of whom remained asymptomatic. Other complications were septicemia byStaphylococcus aureus in 1 patient, transient encephalopathy in 9 patients, and disseminated intravascular coagulation in 1 patient. Conclusion: TIPS appears to be a relatively safe and effective technique in treating complications of portal hypertension in patients with cirrhosis. Shunt obstruction in 31% of our patients probably represents the most important limitation of this technique.

Enhanced urinary excretion of cGMP in liver cirrhosis. Relationship to hemodynamic changes, neurohormonal activation, and urinary sodium excretion

Cyclic guanosine monophosphate (cGMP) has beenproposed to mediate peripheral arterial vasodilation inliver cirrhosis. Nitric oxide and natriuretic peptidesare the main signals for cGMP generation. Variation in urinary cGMP excretion parallels changes inplasma cGMP levels. Our aim was to determine urinaryexcretion of cGMP (UcGMPV) and to investigate itsrelationship to systemic hemodynamics, neurohumoral activity and renal sodium excretion incirrhosis. Urinary excretion of cGMP was measured in 19healthy subjects and 20 patients with alcoholiccirrhosis. Systemic hemodynamic parameters, blood volume(BV), plasma atrial natriuretic factor (ANF), and theendothelium-dependent vasodilator substance P (SP) weredetermined in all patients and in five healthy subjects.Urinary cGMPV was higher in the group of patients (736 pg/min; 50 -3229 pg/min) than incontrols (126 pg/min; 0-1657 pg/min) (P < 0.01). Inaddition, UcGMPV inversely correlated with the systemicvascular resistance and directly with cardiac output, blood volume, SP, ANF, and Pughs score. By Coxregression analysis, only systemic vascular resistanceremained inversely associated with UcGMPV. Inconclusion, urinary cGMP excretion is increased incirrhosis. It is suggested that increased cGMP generationmay be related to the hyperkinetic circulation in humancirrhosis.

Atrial natriuretic factor in cirrhosis: relationship to renal function and hemodynamic changes.

Plasma atrial natriuretic factor concentrations and different hemodynamic parameters, including the evaluation of femoral arteriovenous shunting by measuring the arteriovenous difference of oxygen content (Ca-vO2), were determined in eight healthy subjects and 24 patients with cirrhosis without renal failure (group I: seven patients without ascites, group II: nine patients with ascites and UNaV > 10 mEq/24 h and group III: eight patients with ascites and UNaV < or = 10 mEq/24 h). Atrial natriuretic factor was 34 +/- 4.7 pg/ml in the control group and 44.28 +/- 5.4, 67.89 +/- 8.8 and 84 +/- 10.8 pg/ml in groups I, II and III respectively (p < 0.001. group III vs. I and control and II vs. control). Atrial natriuretic factor directly correlated with cardiac index (p < 0.01), blood volume (p: 0.01), femoral blood flow (p < 0.01) and inversely with systemic and femoral vascular resistances (p < 0.02), Ca-vO2 (p < 0.01), serum albumin (r: -0.61; p < 0.01) and prothrombin index (r: -0.63; p < 0.02). These results indicate that plasma atrial natriuretic factor is increased in patients with cirrhosis, especially in those with advanced disease and marked renal sodium retention. This suggests that in cirrhosis, arteriolar vasodilation and peripheral arteriovenous shunting influence renal function while inducing a state of overflow at the central venous compartment leading to increased atrial natriuretic factor secretion. Increased production of this vasodilatory hormone may thus contribute to the hyperkinetic circulation of cirrhosis.

Estudio de coste-efectividad del empleo de somatostatina para la disminución de pancreatitis agudas post-CPRE

Objetivos Estudios recientes demuestran que la inyeccion intravenosa de somatostatina previa a la practica de una CPRE se acompana de una significativa reduccion de la tasa de pancreatitis aguda post-CPRE. Ante la falta de datos en nuestro medio, hemos querido estudiar el posible beneficio economico de la administracion de somatostatina, obtenido a traves de la disminucion de los costes debidos a las pancreatitis agudas post-CPRE. Material y Metodo Estudio teorico de los costes directos de la pancreatitis aguda post-CPRE, mediante el metodo del “arbol de decisiones” de Markov. Se comparan los costes del grupo pretratado con administracion intravenosa de 3 mg de somatostatina con respecto al grupo control. Se aceptan unas tasas de pancreatitis post-CPRE del 10% en el grupo control y del 3% en grupo con somatostatina. Los costes de los distintos tipos de pancreatitis, sin y con complicaciones y con actuacion quirurgica, se han basado en los pesos por GDR aplicados por el Ministerio de Sanidad y en el Contrato-programa del Servicio Navarro de Salud para 1999. Se ha efectuado un analisis de sensibilidad para precisar a partir de que tasa de pancreatitis post-CPRE se obtendria un beneficio economico en el grupo pretratado con somatostatina. Resultados El coste medio teorico por exploracion fue de 121.640 pesetas para el grupo control y de 105.539 pesetas para los tratados con somatostatina, con un ahorro por caso del 13,26% (16.101 pesetas). El analisis de sensibilidad demuestra que con la premedicacion se obtiene un beneficio economico a partir de tasas de pancreatitis del 4,2% en el grupo control. Conclusiones Con independencia del beneficio clinico que significa la reduccion de pancreatitis post-CPRE, la administracion de somatostatina supone un ahorro de 16.101 pesetas por paciente. Aceptando que la tasa de pancreatitis en el grupo tratado se reduce de manera proporcional, el analisis de sensibilidad pone de manifiesto que con la premedicacion se obtiene un beneficio economico a partir de tasas de pancreatitis del 4,2% en el grupo control.

Influye el posible cansancio del endoscopista en la frecuencia de colonoscopias incompletas y de las lesiones polipoideas diagnosticadas

INTRODUCTION Nowadays, the possible effect of endoscopist fatigue on the results of colonoscopies is under discussion. We aimed to analyze possible differences in cecal intubation and the polyp and adenoma detection rate, depending on whether colonoscopies were performed at the beginning or at the end of the daily endoscopy session and to analyze the influence of the queue position on the detection rate. PATIENTS AND METHODS A retrospective study was performed with 1,000 ambulatory and consecutive colonoscopies, divided into 2 groups: «early» and «late» procedures. A total of 95 colonoscopies were excluded due to poor colon cleansing. After confirming that patient characteristics were homogenous in the two groups, we compared the frequency of complete colonoscopies and the polyp and adenoma detection rate. Possible differences between the 2 groups in the polyp detection rate according to the colonoscopy schedule were analyzed. RESULTS The overall polyp and adenoma detection rates were 44.2 and 30.5%, respectively, with no significant differences among 13 different endoscopists; polyps: p = 0.21; adenomas: p=0.63. No significant differences were found between the «early group» (n= 532) and the «late group» (n = 373) in the rates of complete colonoscopies [97.2 vs 99.4% (p=0.92)], the polyp detection rate [45.9 vs 41.8% (p=0.23)], the adenoma detection rate [30.8 vs 30% (p=0.80)] or the serrated adenoma rate [2.1% vs 1.6% (p=0.62)]. The lesion detection rate did not vary in relation to the «queue position»: polyps [p = 0.60, and adenomas: p = 0.83. CONCLUSIONS In our series, endoscopist fatigue at the end of the day had no influence on the complete colonoscopy rate or on the polyp and adenoma detection rate. There were no differences in the number of polypoid lesions detected according to the timing of the colonoscopy schedule.

Lesiones gastrointestinales y características de las hemorragias digestivas agudas en los pacientes anticoagulados con acenocumarol

UNLABELLED In the last few years, the number of anticoagulated patients has significantly increased and, as a consequence, so have hemorrhagic complications due to this therapy. We analyzed gastrointestinal (GI) bleeding because it is the most frequent type of major bleeding in these patients, and we hypothesized that they would have lesions responsible for GI bleeding regardless of the intensity of anticoagulation, although excessively anticoagulated patients would have more serious hemorrhages. OBJECTIVES To study the characteristics of anticoagulated patients with GI bleeding and the relationship between the degree of anticoagulation and a finding of causative lesions and bleeding severity. PATIENTS AND METHODS We prospectively studied 96 patients, all anticoagulated with acenocoumarol and consecutively admitted to hospital between 01/01/2003 and 09/30/2005 because of acute GI bleeding. We excluded patients with severe liver disease, as well as nine patients with incomplete details. RESULTS The incidence of GI bleeding requiring hospitalization was 19.6 cases/100,000 inhabitants-year. In 90% of patients, we found a causative (85% of upper GI bleeding and 50% of lower GI bleeding) or potentially causative lesion, and 30% of them required endoscopic treatment, without differences depending on the intensity of anticoagulation. No relationship was found between the type of lesions observed and the degree of anticoagulation in these patients. Patients who received more intense anticoagulation therapy had more severe hemorrhages (23% of patients with an INR ≥4 had a life-threatening bleed versus only 4% of patients with INR <4). CONCLUSIONS We found an incidence of 20 severe GI bleeding episodes in anticoagulated patients per 100,000 inhabitants-year, with no difference in localization or in the frequency of causative lesions depending on the intensity of anticoagulation. Patients receiving more intense anticoagulation had more severe GI bleeding episodes.

Efectividad de los antivirales de acción directa de segunda generación en el tratamiento de la hepatitis C crónica

Background. Second-generation direct-acting antivirals (DAA) have shown high sustained virologic response (SVR) for the treatment of chronic hepatitis C in clinical trials. The objective of this study is to estimate DAA effectiveness in treatment of this disease. Methods. Hepatitis C virus (HCV) monoinfected patients and HCV-human immunodeficiency virus (HIV) coinfected patients who started interferon-free DAA based regimens during 2015 were included. The primary effectiveness outcome was SVR, defined as an undetectable viral load 12 weeks after the end of treatment. Results. A total of 293 patients were enrolled, and 52 (17.7%) were HIV coinfected. HCV 1b genotype was the most prevalent in monoinfected patients (41.5%) and 1a in HIV coinfected patients (40.4%). The proportion of cirrhosis was higher among HIV coinfected patients (69.2% vs 41.1%; p<0.0001), mostly Child-Pugh A. SVR was achieved by 96.9% of patients (284/293), in an intention-to-treat analysis (CI 95%: 94.9-98.9%), in which just 4 people had virologic failure. Both naive and pretreated patients had SVR higher than 95%, and in most of subgroups, according to the presence of cirrhosis, HIV coinfection and HVC genotype, effectiveness rates were near or above 90%. Conclusions. DAA are highly effective, with similar or higher rates of SVR than that found in clinical trials, and even among difficult to treat populations.